The ultimate goal of this research is to use quantitative in vitro methods to investigate the potential mutagenic effects of regimens used in treatment of pediatric cancer patients. The immediate goals are 1) to detect the frequency of phenotypically variant 6-thioguanine- (6-TG)-resistant peripheral blood lymphocytes in pediatric cancer patients, and 2) to determine whether 6-TG-resistance results from somatic mutation. Thioguanine-resistant variant frequency is measured using the short-term autoradiographic method of Albertini (Mut. Res. 61:353, 1979). We have studied prospectively and prospectively-retrospectively 93 specimens in 58 healthy children or adults, and 101 specimens in 64 patients with Hodgkin's disease or sarcomas before, during, and after receiving chemotherapy and radiation therapy. In healthy controls, the mean variant frequency of 6-TG-resistant lymphocytes is 4.9 times 10 to the minus 5th power. In Hodgkin's patients the mean variant frequency is 4.2 times 10 to the minus 4th power before therapy, 7.7 times 10 to the minus 3rd power during therapy, and 4.4 times 10 to the minus 4th power after therapy. In sarcoma patients, the mean variant frequency is 5.6 times 10 to the minus 4th power before therapy, 1.8 times 10 to the minus 3rd power during therapy, and 8.8 times 10 to the minus 5th power after therapy. In some Hodgkin's disease patients, abnormally high variant frequencies persist indefinitely. We are developing 6-TG resistant lymphoblastoid lines to determine whether 6-TG resistance results from mutation of the gene for hypoxanthine-guanosine-phosphoribosyl transferase.